Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutationsin a population-based series of early-onset breast cancer

Background: BRCA1 and BRCA2 are the two major susceptibility genes involved in hereditary breast cancer. This study was undertaken to provide reliable population-based estimates of genetic influence and to characterize the na ture and prevalence of BRCA1 and BRCA2 germline mutations in early-onset br east cancer. Methods: In a series comprising all women diagnosed with breas t cancer under the age of 41 years in southern Sweden during 1990 through 1 995 (n = 262), family history of cancer was evaluated in 95% (n = 250) of t he case subjects and germline mutations in BRCA1 and BRCA2 were analyzed in 89% (n = 234). All statistical tests were two-sided. Results: A total of 9 7 case subjects had at least one first- or second-degree relative with brea st or ovarian cancer; 34 (14%; 95% confidence interval [CI] = 9.6% to 18 %) cases had at least two first- or second-degree relatives, 22 (8.8%; 95% CI = 5.3% to 12%) had one first-degree relative, and 41 (16%; 95 % CI = 12% t o 21%) had one second-degree relative with either cancer. If two females af fected with breast or ovarian cancer who were related through an unaffected male were also defined as first-degree relatives, then a higher number of case subjects, 120 (48%; 95% CI = 42% to 54%), had at least one first-degre e or second-degree relative with breast or ovarian cancer. Sixteen (6.8%; 9 5% CI = 4.0% to 11%) BRCA1 mutation carriers and five (2.1%; 95 % CI = 0.70 % to 4.9%) BRCA2 mutation carriers were identified. Among case subjects wit h one first- or more than one first- or second-degree relative with breast or ovarian cancer, BRCA mutations were more frequent (P < .001) than among the case subjects without this degree of family history. BRCA mutations wer e also statistically significantly more common among women with bilateral b reast cancer than among women with unilateral breast cancer (P =.002). BRCA mutations were more common among younger case subjects than among older on es (P =.0027). Conclusions: Almost half (48%) of women in southern Sweden w ith early-onset breast cancer have some family history of breast or ovarian cancer, and 9.0% of early-onset breast cancer cases are associated with a germline mutation in BRCA1 or BRCA2. Mutation carriers were more prevalent among young women, women with at least one first- or second-degree relative with breast or ovarian cancer, and women with bilateral breast cancer.